Method for the production of isoindoles



United States Patent 3,385,865 METHOD FOR THE PRODUCTION OF ISOINDOLESGerlinde Metzler, Stamford, Conn., assignor to American CyanarnidCompany, Stamford, Comp, a corporation of Maine No Drawing. Filed Dec.13, 1965, Ser. No. 513,580

Claims. (Cl. 260-326.1)

ABSTRACT OF THE DISCLGSURE A process for the preparation of isoindolecompounds comprising reacting an orthodiketone with an excess of amono-N-substituted ammonium formate, at from about 175 C. up to about250 C. for a period of about ten hours up to about seventy-two hours.

The present invention relates to solution phase electroluminescence. Theinvention includes the discovery of a new class of compounds, a processfor making the compounds, and a new class of compositions and process ofuse thereof.

It has been found, pursuant to the instant discovery, that anunexpectedly high degree of visible electro-luminescent emission may begenerated by applying alternating current, at a suiiicient voltage, tothe electrodes, e.g., platinum, mercury, or the like, of an electrolyticcell in an inert solvent containing a particular class of fluorescentorganic compounds of this invention and a suitable supportingelectrolyte. The new compounds are also useful as battery depolarizers,dyes, chemiluminescent substances, etc.

I have discovered that a high order of luminescence can be obtained froma new class of electrochemiluminescent fluorescers of the isoindoleformula:

(I) A E I D B in which X is a member selected from the group consist ingof either substituted or non-substituted alkyl and aryl substituents, inwhich A and B are each either a substituted or a non-substituted arylsubstituent, and in which each of C, D, E, and F is selected from thegroup consisting of hydrogen and either substituted or nonsubstitutedaryl substituents. Each of the above alkyl and aryl substituents may beany substituent which does not counteract theelectrochemiluminescent-fluorescent property of the compounds of thisinvention. Typical aryl substituents include phenyl, l-naphthyl,l-anthracenyl, biphenyl, 2- naphthyl, 3-phenyl, p-cyanophenyl,p-alkoxylphenyl, pdialkylaminophenyl, p-nitrop'henyl, 2-anthracenyl,9-anthracenyl, phenanthryl, 3 and 4 pyrenyl, tetracenyl, singly ormultiply substituted alkoxy-aryl such as methoxyphenyl,dialkylamino-aryl such as dimethylaminophenyl, and the like. However, X,A and B may not be 3 and 4 pyridyl, p-cyanophenyl, nor p-nitrophenyl.Typical alkyl substituents include methyl, ethyl, propyl, etc., andtheir substituted forms, for electrochemiluminescence. The fluorescentcompounds are characterized by (1) a polarographic oxidation statehaving cation radical of unex- "ice pectedly superior stability ascompared to previously known electrochemiluminescent fluorescers, (2) anunexpectedly high fluorescence-efliciency, and (3) an unexpectedlysuperior long-lifetime of electrochemiluminescence. The lifetime, forexample, of some compounds of this invention is more than four timesthat of the best isoenzofuran (illustrated in the copending applicationSer. No. 509,148, filed Nov. 22, 1965) and about nine times that ofrubrene. These properties are illustrated in the Table I below.

In order to obtain the electrochemiluminescence, it is critical that theelectrochemiluminescent fluorescent isoindole compound of this invention'be present in a concentration of at least about one millimolar up toabout 20 lIIlilllIIlOlGS. For the preferred results, it is critical thatat least about 5 to about 10 millimoles be employed. The electrolyte mayrange from about 0.01 M to about 1.0 M, the preferred results requiringat least about 0.1 M.

Typically, dimethylformamide (DMF) solvent containing 2 l0 mole of thefluorescent compound of this invention, and 0.1 mole oftetrabutylammonium perchlorateas the supporting electrolyte is a systemwhich will emit light, without :any appreciable consumption of thesolution components of the system as compared to prior systems, whenplaced in an electrolytic cell containing electrodes and -cyclealternating current applied to the electrodes. Visible light is emittedat or near each electrode surface as long as alternating current ofsuflicient voltage is applied.

Pursuant to the instant discovery, therefore, a method of generating auseful, visible, electroluminescent emission in an electrolytic cell hasbeen found which comprises subjecting a fluorescent compound of thisinvention to an alternating current through at least two electrodes inan intimate contact with a medium comprising an inert solvent, afluorescent organic compound of this invention, and a supportingelectrolyte, said alternating current being at a suflicient voltage(potential) in at least one electrode to convert said fluorescentorganic compound to its corresponding oxidized or reduced state, bygiving up or taking on at least one electron, and said alternatingcurrent providing suflicient potential (voltage) change on reversal ofthe alternating cycle to provide an amount of energy about sufiicient toultimately transform (regenerate) said fluorescent organic compound toits original oxidation state but in its singlet excited state. Thecompound rapidly returns to its ground (non-excited) state by theemission of light.

As indicated above, the fluorescent organic compound is eitheralternately oxidized to an oxidized state (i.e., a cation radical), inwhat is the anodic excursion of the applied potential and reduced to theexcited state of the fluorescent organic compound in what is thecathodic excursion of the applied potential; or the fluorescent organiccompound is reduced to a reduced state (i.e., an anion radical) in whatis the cathodic excursion of the applied potential and oxidized to theexcited state of the fluorescent organic compound in what is the anodicexcursion of the applied potential. Fluorescent compounds which emit redlight upon excitation require at least anodic or cathodic voltageexcusion and, consequently, the least voltage change at an electrode toprovide visible light. On the other hand, fluorescent compounds whichemit blue light upon excitation require greater anodic or cathodicexcursions and higher voltage change at the electrode.

The upper and lower limits of the instantaneous potential applied to theelectrode required to produce light Will depend on the fluorescentorganic compound used. Thus either the upper limit of the appliedpotential must be sufficiently positive to convert the fluorescentorganic compound to an oxidized state or the lower limit of thepotential applied to the electrode must be sufiiciently negative toconvert the fluorescent organic compound to a reduced state. Moreover,the potential difference between the upper and lower values of theinstantaneous applied potential must be at least about sufficient toprovide enough energy to produce said fluorescent organic compound inits singlet excited state.

Broadly, the voltage requirement may be defined as ranging from about 5volts to volts. The optimum and therefore preferred results are obtainedwhen a voltage of at least about 6 v. up to not more than about 7 v. isemployed.

In general terms, the process described above requires only electrontransfer to a cation radical or electron transfer from an anion radicalin an electrolyte cell where electron transfer occurs over a sufficientpotential to provide an excited state, and where the resulting excitedstate or a subsequently formed excited state is capable of fluorescentemission of light. The general process is described in Equations 1 and 2below where A+ and A refer to a cation radical and an anion radicalrespectively, E refers to an electron, and A" refers to an excited stateproduced by electron transfer.

or by an indirect route, typically as shown in Equation 4 below.

The potential difference required by the indirect route normally islower than that required by the direct route.

Generally, the potential difference between the upper and lower limitsof the instantaneous applied voltage must exceed about 1.5 volts.

Potentials (relative to a standard electrode, such as the saturatedcalomel electrode), required to oxidize or re duce organic compounds ofthe type contemplated herein can be easily measured by standardpolarographic techniques. Cf. I. M. Kolthoff and J. J. Lingane,Polarograph, 2nd ed., 1952, Interscience Publishing, ew York, NY.Likewise minimum energy required for converting organic compounds of thetype contemplated herein to their singlet excited states are easilymeasured by such techniques as absorption or emission spectroscopy. Cf.S. P. Mason, Molecular Electronic Absorption Spectra, Quarterly Review,15, 287 (1961).

The process of the present invention has multiple uses in the fields ofillumination, information display, etc. For instance, an electrolyticcell is in essence a light bulb, the electrolytic cell comprising astoppered transparent bottle having two electrodes therein, the ends ofwhich are immersed in the fluorescnet-solvent-electrolytc system. Ifdesired, the bulb-shaped cell could be replaced by a tubular, orcube-shaped cell, or by any other design desired. Likewise, multiplepairs of electrodes may be used in any given cell, each pair operatingindependently, if desired. Still other uses will be discussed in greaterdetail hereinafter.

Obviously, as indicated hereinabove, the solution system as well as thenature of the electrode determine the upper limit of the potentialdifference.

Insofar as the frequency of the applied alternating voltage isconcerned, it can range from a few cycles per minute up through theaudio range and beyond.

Broadly the frequency may range from about 50 to about 200 cycles persecond. To obtain the optimal (and therefore the preferred) results, thefrequency should be at least about 60 cycles per second.

Temperature does not appear to be critical, the temperature normallyranging from zero up to about 60 C.

A wide variety of supporting electrolytes may be employed herein toeifect the invention. It is essential that these electrolytes do nothinder to any substantial degree the necessary anodic or cathodicexcursion, for instance, and thus prevent conversion of the organicfluorescent compound to its excited state. it will be recognized by theperson skilled in the art that a non-interfering electrolytic for oneorganic fluorescent compound may interfere with another organicfluorescent compound, and vice versa. Obviously, therefore, it is Withinthe purview of the instant discovery and within the skill of a chemistto employ an electrolyte which is compatible with the organicfluorescent compound employed. The electrolyte should likewise beelectro-inactive over the potential range required for the luminescentreaction, it should provide satisfactory conductivity, and it should notquench the luminescence.

Typical suitable electrolytic cations are tetra-alkyl (lower) ammoniumions, alkali metal ions, alkaline earth ions, and the like. Typicalanions are perchlorate ions, hexafluoroarsenat'e ions,hexafluoraphosphate ions, chloride ions, bromide ions, and the like.Thus, typical compounds include tetraethylammonium bromide,tetraethylammonium perchlorate, tetra-n-butyl ammonium perchlorate,lithium bromide, sodium perchlorate, tetramethylammoniumhexafiuoroarsenate, tetrabutylammonium tetraphenyl borate, calciumperchlorate, tetrapropyl ammonium hexafluorophosphate, lithium aluminumchloride, tetrabutyl ammonium bromide, etc.

insofar as solvents are concerned, a wide variety of these may beemployed. In fact, any substantially inert organic or inorganic solventfor the organic fluorescent compound and electrolyte, which solvent issufliciently non-protonating and irreducible to preserve the desireddegree of reversibility (i.e., it should provide a lifetime of theradical ion at least equivalent to the reciprocal of the frequencyemployed) is satisfactory provided it is rendered conducting by theaddition of an electrolyte of the type contemplated herein.

Typical solvents are the following aprotic solvents: nitriles, such asacetonitrile: sulfoxides, such as dimcthylsulfoxide, others, such astetrahydrofuran dioxane, diethyl ether, 1,2-dimethoxyethane, and thelike; amides, such as dimethylformamide (i.e., DMF): carbonates, such aspropylene carbonate; nitronlkanes, such as nitromethane; dialkylsulfites, such as dimethylsulfite; and other like solvents. Thepreferred solvent, however, is DMF.

It is not necessary that these solvents be anhydrous, since up to about10% water has been present in some cases without interfering with theemission of visible light. The person skilled in the art will recognizethat numerous other substantially inert organic and inorganic solvents,even though not essentially or substantially aprotic, are compatiblewith the process and solution system and are substantially notfluorescence quenchers. Solvent mixtures may likewise be employed.

In conjunction with the excited state referred to hereinbefore, itshould be noted that the energy of an excited state is an easilymeasured experimental value. For example, the energy difference betweena first excited singlet and its corresponding ground state is defined bythe frequency of the first absorption band in the ultraviolet or visiblespectrum of the ground state species.

The physical energy released by a reaction is also an experimentalquantity. For instance, the energy of a reaction of the type given inthe specific embodiment described above, can be determined bypolarographic measurements and other procedures well known to thephysical chemist.

Thus, the operable limits of electroluminescence are capable ofindependent measurement and of clear definition in terms of physicalcharacteristics. Consequently, generating electroluminescent emission bythe process contemplated herein can be accomplished by first recognizingthe known physical characteristics of the fluorescent organic compound,as well as the physical characteristics of the inert solvent and theelectrolyte to be used. It has been found, however, that the potentialchange during the electrode excursion can be several tenths of a voltless than that required to provide the energy of a singlet excited stateand still be sufficient to generate noticeable light emission. Bestresults are generally obtained, however, when the calculated singletexcitation energy or more is provided. It should also be noted that thevoltages referred to are exclusive of additional voltages that might berequired to overcome the electrical resistance of thesolvent-electrolyte employed.

The temperature at which the above-defined electrochemiluminescentprocess of the present invention is carried out is not critical; veryexcellent results have been achieved at ambient temperatures. For bestresults the solvent employed is deaerated, such as by bubbling nitrogen,or the like, therethrough, thus providing improved conditions andhelping to insure a substantially inert solvent.

It should be noted that the isoindole compounds of this invention, asfully defined above, cannot be made by conventional methods (for makingisoindoles) as described in the literature. Accordin ly, a novel processfor producing the isoindoles of this invention is the reacting of anorthodiketone with an excess of a mono-N-substituted ammonium formate,is from about 175 C. up to about 250 C. for a period of about ten hoursup to about seventy-two hours. The preferred temperature, critical toobtain the preferred results, is from about 190 C. up to about 215 C.The preferred ratio of the formate compound to the ketone compound is atleast about 421, this minimum ratio being critical to obtain thepreferred results. Also, to obtain the preferred results, it is criticalthat the reaction mixture be substantially in the absence of a solvent.A reaction time of fifteen to twentyfour hours has proven to besatisfactory. Typical of the orthoketones employable in the process is1,4-diphenyl- 2,3-dibenzoylbenzene of the formula:

Representative (but not exclusive) examples of orthoketones, in theorder of preference, are: 1,4-diphenyl- 2,3-di-p-anisoylbenzene;1,4-diphenyl, 2,3-dibenzoylbenzene;1,4-di-p-anisyl-2,3-dibenzoylbenzene; 1,4-di-p-anisyl-2,3-di-p-anisoylbenzene; 1,4 di-x-naphthyl-Z,3-dibenzoylbenzene; and1,4-di-1-pyrenyl 2,3 dibenzoylbenzene. Typical representative (but notexclusive) mono-substituted ammonium formates are those in which the N-substituent is methyl, ethyl, n-propyl, isopropyl, phenyl, naphthyl,pyrenyl, and the like, in the order of preference. Alkyl N-substituentsare preferred to aryl substituents.

The brightness and lifetime of electrochemiluminescence depends on theinterplay of many variables. We are not sure that we know them all.

One of these variables seems to be the voltage. A characteristicvoltage, commonly 7-8 v., although 5-10 v. is probably the ultimaterange.

Another variable is the frequency of the imposed A.C. current. Eachcompound may well have its own characteristic A.C. frequency for maximumbrightness.

Another factor is the wavelength of maximum ECC emission. The closerthis is to the eyes maximum sensitivity, the brighter the light willappear. A rough correlation of this is observed in the isoindoles. Thesecompounds all emit at the same wavelength maximum as their fluorescencespectrum maximum. This is not true with all electrochemiluminescentsubstances.

A further factor is the concentration and solubility of the compound. InDMF the desired concentration appears to be about 10 mm. Many otherwisepromising compounds (rubrene) are not that soluble.

Fluorescence efficiency is also a factor. Of a given number of moleculesthat reach the exicted state only a fraction will, in dropping down tothe ground state, emit light that will ultimately be seen by the viewer.This fraction is in turn determined by several factors.

The nature of the solvent, electrolyte electrodes and geometry of thecell will also effect the brightness and lifetime. DMF, Bu NClO and Ptgauze spaced as closely as possible have so far proven most desirable.

Stability of the oxidation and reduction products of the fluorescerseems to be involved especially with the lifetime of the ECL event sincethe voltage range to which the molecule is subjected is great enough forit to undergo both oxidation and reduction by electron transfer.Reaction or decomposition of the oxidation rand/or reduction products ofthe fiuorescer results in loss of tluorescer.

Table I below illustrates the optimum stability, brightness, lifetime,and other physical properties. Table I demonstrates many of the pointsindicated here.

The following Examples I and II illustrate the method of preparation ofthe novel compounds of this invention, and Table I illustrates theresults upon evaluation of several isoindoles of this invention, andcompares the results with prior electrochemiluminescent compounds suchas rubrene and such as the isobenzofuran compounds of the copending US.Ser. No. 509,148, filed Nov. 22, 1965.

The following examples and Table I are intended only for purposes ofillustration and do not limit the scope of the invention except asstated, and except as the appended claims =are limited.

"Example I N methyl 2,7 di p anisyl 3,6 di phenylisoindole is preparedby refluxing at about 210 to 215 C. 4 grams of1,2-di-p-anisoyl-3,6-di-phenylbenzene with 15 ml. of mono methylammoniumformate for about 24 hours, under an inert atmosphere such 13S nitrogen,followed by cooling, filtering multiple recrystallization from a liquidsuch as benzene, to obtain a yield of about 1.46 grams (40%) and havinga melting point of about 237-239 C. The properties of the compound areillustrated in Table I.

Example If N-methyl-2,3,6,7-tetraphenylisoindole is prepared byrefluxing at about to C. about 3.5 grams of1,2-dibenzoyl-3,6-diphenylbenzene in admixture with a four-fold excess(by weight) of monomethylammonium formate, for about 15 hours, followedby cooling the yellow-green crystals, adding a minor amount of methanol,filtering, and multiple (twice) recrystallization, to obtain a yield ofabout 1.5 grams (35%) having of about M.P. 281-283 C. The properties ofthe compound are illustrated in Table I.

n r TABLE I Voltage Frequency Wave Ooncen- Bright- For For length ofnation Flno- Stability Stability ness Lifetime Compound Maximum Maximumrvlaximunr For rescouco of i0. Oxid. of in. Red. (maximum) (maxinnun)Bright BrightllGL Maximum Eilieiciv Prod, see. Prod, see. foo min. ncss,v. noss, c.p.s. Emission, Brighlcy, RE. lamberts In noss, inIvl.

N-methv1-2,3,G,7-tctra phen '1 8 185 2 .53 15 2 3 8 250diphenylisoindoleu s 515 5 .52 15 2 7 2 1, s Rnbrene 6 60 550 1 2 .17 155 200 2,3,0,7-tctraphonyi isobonzoinran 8 120-130 510 6 .51 1.0 10 22405 2,7-(liphonyl-3,0-di-pmethoxypheuylisobenzoiuran 8 510 3. 0 2 3 22,3,6,7-totrap-rnethoxyphenylisobenzoiuran 7 530 0. 5 15 10 1 Sat. 25111M.

The last two columns in the table clearly indicate in terms of maximumbrightness and lifetime the compounds which are most desirable. Furtherimprovements in lifetimes in these systems can be anticipated when themany variables which affect this property are fully explored. Thestability of the isoindole compounds of this invention is clearlysuperior.

Clearly the instant discovery encompasses numerous modifications withinthe skill of the art. Consequently, while the present invention has beendescribed in detail with respect to specific embodiments thereof, it isnot intended that these details be construed as limitations upon thescope of the invention, except insofar as they appear in the appendedclaims.

What is claimed is:

1. A process for the preparation of an isoindole of the formula:

C A l E A wherein X is a substituent selected from the group consistingof lower alkyl, phenyl, l-naphthyl, l-anthracenyl, biphenyl, Z-naphthyl,3-phenyl, palkoxyphenyl, pdialkylaminophenyl, Z-anthracenyl,9-anthracenyl, phenanthryl, 3- and 4-pyrenyl, tetracenyl, alkoxyphenyland dialkylamino-phenyl;

A and B are substituents selected from the group consisting of phenyl,l-naphthyl, l-anthracenyl, bip-henyl, Z-naphthyl, 3-phenyl,p-alkoxyphenyl, p-dialkyl aminophenyl, Z-anthracenyl, 9-anthraeenyl,phenanthryl, 3- and 4-pyrenyl, tetracenyl, alkoxyphenyl anddialkylaminophenyl; and

C, D, E and F are substituents selected from the group consisting ofhydrogen, phenyl, l-naphthyl, 3-phenyl, p-alkoxyphenyl, p-cyanophenyl,p-dialkylaminowith a mono-substituted ammonium formate wherein theammonium moiety has the formula:

wherein A, B, C, D, E, F and X are as above defined, at from about C. toabout 250 C. for a period from about ten hours to about seventy-twohours.

2. A process according to claim 1 in which said reacting is carried outat from about C. up to about 215 C.

3. A process according to claim 1 in which said formate and said ketoneare in a ratio of at least about 4:1 by weight.

4. A process according to claim 1 in which said reacting is carried outsubstantially in the absence of a solvent.

5'. A process according to claim 4 in which said reacting is carried outat from about 190 C. up to about 215 C., and said formate and saidketone are in a ratio of at least about 4:1 by weight.

References C to UNITED STATES PATENTS 3,007,939 11/1961 Norton 260-326.l

NICHOLAS S. RIZZO, Primary Examfl'ler.

M. OBRIEN, I. A. NARCAVAGE, Assislazzl Examine/s.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent N0.3,385,865 May 28, 1968 Gerlinde Metzler It is certified that errorappears in the above identified patent and that said Letters Patent arehereby corrected as shown below:

Column 3, line 17 "6 v. should read 6 V. same line 17, "7 v." shouldread 7 V. Column 6, line 4, "7-8 v." should read 7-8 V. same line 4,"5-10 v." should read 5-10 V. line 18, "10 mm." should read 10 mM.Columns 7 and 8, TABLE I, footnote thereof, Sat." should read -Sat.

Signed and sealed this 3rd day of March 1970.

(SEAL) Attest:

Edward M. Fletcher, Jr. WILLIAM E. SCHUYLER, JR.

Attesting Officer Commissioner of Patents

